First Real-World Data of Olaparib Combination Treatment with Abiraterone and Prednisone or Prednisolone in First-Line Metastatic Castration-Resistant Prostate Cancer (mCRPC): Descriptive Analysis of 154 Patients Enrolled in the Early Access Program in France.

Background: Olaparib, a poly ADP-ribose polymerase inhibitor, was approved by the European Commission in December 2022 and for which the Health for technology Assessment (HtA body) issued a favorable opinion for reimbursement in France on 5 April, 2023, following the results of the PROpel phase III clinical trial, for the first-line treatment of metastatic castration-resistant prostate cancer in combination with abiraterone and prednisone or prednisolone in adult men for whom chemotherapy is not clinically indicated.

Objective: This publication aimed to report the first real-world data of patients with metastatic castration-resistant prostate cancer who received a combination of first-line olaparib with abiraterone, plus prednisone or prednisolone in the funded Early Access (fEA) for olaparib in France, from 30 March, 2023, to 25 September, 2024.

Methods: Eligible patients were adult men with first-line metastatic castration-resistant prostate cancer. Olaparib 300-mg twice-daily tablets was given in combination with abiraterone plus prednisone or prednisolone regardless of the homologous recombination repair gene mutation status. Characteristics of the population, treatment duration, reasons for discontinuation, and safety data were collected during the fEA period. Patients could continue to receive olaparib after the end of the fEA.

Results: A total of 84 physicians spread over 72 hospitals in metropolitan France requested a fEA for 176 patients, 154 (87.5%) of whom were eligible to be included in the early access program. In total, 118 (76.6%) patients had an unknown homologous recombination repair status. Half of the patients (76, 49.7%) had very aggressive cancer with a Gleason score of 8 while 11 (7.2%) of them had a low-grade cancer with a Gleason score of 6 at the diagnosis. The most common metastatic sites were bone (107 patients, 69.5%) and distant (60, 39.0%) or regional (42, 27.3%) lymph nodes. Among the 154 patients, 84 (54.5%) had medical history, 47 (56.0%) of whom had arterial hypertension. All included patients had received at least one prior treatment prior to the metastatic castration resistance stage. Most patients (145, 94.2%) had received androgen suppression and 70 (45.5%) had been treated with androgen receptor pathway inhibitors. Of the 154 patients, 153 (99.4%) had at least one concomitant treatment with abiraterone and prednisone or prednisolone. Data confirming administration of olaparib treatment were provided for 149 patients (exposed patients), of whom 140 (94.0%) received olaparib at initiation at the dose of 300 mg twice daily. Fifty-seven patients experienced a total of 60 adverse events (36 serious adverse events and 24 non-serious adverse events). Over this period, three fatal and five life-threatening events were reported. The three fatal adverse events were one death assessed as a suspected adverse reaction (pancytopenia) and two deaths assessed as unrelated to olaparib: one attributed to disease progression and one to suicide. Because of adverse events, dose reductions were made in five patients, treatment was temporarily interrupted in one patient and discontinued in 20 patients.

Conclusions: These are the first results describing the real-world use of olaparib in France in prostate cancer. Most patients included in the fEA had generally similar characteristics as the patients randomized in the PROpel clinical trial (NCT03732820) and initiated at the standard dose of 300 mg twice daily. No new safety signals were reported in this real-world patient population. The analyzed data did not modify the benefit-risk balance of olaparib.